Chiral phosphine ligands such as (1) and (2) ##STR1##
and the opposite enantiomers thereof, have been shown to be effective in palladium(0)-catalysed asymmetric allylic substitution reactions. For a review, see Trost and Van Vranken, Chem Rev. (1996) 96: 395. See also U.S. Pat. No. 5,739,396.
Such catalysts are eminently suitable for industrial applications, especially for the provision of chiral pharmaceutical intermediates such as phthalimidovinyl glycinol, in high enantiomeric purity. For this purpose, and in other industrial applications such as flavour and fragrance fine chemicals, the development of manufacturing processes requires in turn large amounts of a ligand such as (1) or (2), e.g. in kilogram quantity or greater. Thus, there is a requirement for efficient and scaleable methods for synthesis of such ligands.
A key intermediate in the synthesis of these ligands is 2-diphenylphosphino-1-naphthoic acid and derivatives thereof. Several processes for the synthesis of arylphosphines from aryl triflates have been described in the literature.
For example, WO-A-9312260 and U.S. Pat. No. 5,739,396 disclose the reaction of trimethylsilyldiphenylphosphine, an aryl iodide and bis(benzonitrile)palladium dichloride in toluene at reflux. Trimethylsilyldiphenylphosphine is expensive and not readily available. This procedure gives only moderate yields (60%) and requires silica chromatography for purification of the product. Bis(benzonitrile)palladium dichloride is also expensive, and a high catalyst loading is used (5 mol %).
Another known process comprises the reaction of an aryl triflate with chlorodiphenylphosphine, a reductant (zinc) and a nickel catalyst in DMF at 100.degree. C.; see Ager et al, Chem. Commun. (1997) 2359. This procedure typically requires a high catalyst loading (4-10 mol %) and can involve prolonged heating at reflux. The nickel catalyst is highly toxic and, as well as considerations for operator safety and residue disposal, filtration through a plug of silica is typically required to remove the catalyst.
Cai et al, J. Org. Chem. (1994) 59:7180-1, and U.S. Pat. No. 5,399,771 disclose the preparation of BINAP using the appropriate aryl triflate with diphenylphosphine. The preferred catalyst is nickel, palladium catalysis giving no reaction al all. Cai et al reports that DMF is the only satisfactory solvent. A chelating phosphine was also present.
Gilbertson et al, J. Org. Chem. (1996) 61:2922-3, discloses the palladium-catalysed conversion of aryl triflates, specifically tyrosine derivatives, to the corresponding aryl diphenylphosphines, by reaction with diphenylphosphine. The solvent is DMSO. It is reported that the reaction does not take place in DMF, using palladium. The Supplementary Material shows that 5 mol % of each of the catalyst Pd(OAC).sub.2 and 1,4-bis(diphenylphosphino)butane, i.e. a chelating phosphine, are used. Isolation of pure aryl diphenylphosphine products requires conversion to the corresponding phosphine sulfide, column chromatography and desulfurization with Raney nickel.
Reaction of diphenylphosphine, a base, palladium catalyst and aryl iodide (or bromide) also gives the corresponding triarylphosphine; see Werd et al, J. Organomet. Chem. (1996), 522: 69. For the synthesis of ligand (1) or (2), however, a 2-iodo- or 2-bromo-1-naphthoic acid derivative is not readily accessible.